Lung cancer is the most common cancer among males in India, with high mortality [2]. The initially asymptomatic course and lack of reliable screening methods lead to delay in diagnosis with the result that most of the patients present in the advanced stages of the disease. Many international studies have yielded variable results in prognostic factors that predict treatment outcomes in these patients.

In a study, 1,052 eligible patients with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party (ELCWP) were enrolled to determine the prognostic value for survival of various pretreatment characteristics in patients with non-resectable non-small-cell lung cancer. They prospectively collected 23 variables and found that disease extent, Karnofsky performance status, WBC and neutrophil counts, metastatic involvement of skin, serum calcium level, age, and sex were significant prognostic factors for survival [7].

In 2007, a study was conducted on 203 patients with NSCLC who were enrolled in a phase III trial conducted by the Hoosier Oncology Group and US Oncology between 2002 and 2006. Eligible patients had untreated stage III NSCLC, forced expiratory volume in one second (FEV1) ≥ 1 liter, baseline performance status of 0/1, and weight loss < 5% in 3 months preceding the trial. Univariate analysis, Cox proportional hazards regression, and parametric accelerated failure time models were performed to identify the factors that affected survival duration.

Variables analyzed included age (< 70 years vs. ≥ 70 years), sex, ethnicity, body mass index, performance status (0 vs. 1), FEV1 (> 2 L vs. 1-2 L), smoking status (current vs. never/former), hemoglobin (Hb) level, use of positron emission tomography scan in staging, and stage (IIIA vs. IIIB). The univariate analysis showed that Hb levels ≥ 12 were associated with improved survival (P = .033).

This analysis suggests that FEV1 > 2 L and higher pretreatment Hb values are associated with improved OS in patients with stage III NSCLC [5].

In 2008, a study conducted on 320 NSCLC patients found that squamous histology, number of metastatic sites >2, presence of bone, brain, liver, and contralateral lung metastases, and elevated leukocyte count in peripheral blood were all statistically significant prognostic factors in univariate analyses. In contrast, the other tested variables (sex, stage, age, presence of adrenal gland, and skin metastases) were not. Subsequently, a multivariate Cox's regression analysis identified PS 2 (P < 0.001, hazard ratio 2.57), elevated leukocyte count (P < 0.001, hazard ratio 1.79), squamous histology (P = 0.005, hazard ratio 1.45), and presence of brain metastases as independent prognostic factors for poor survival. Leukocyte count was a more decisive factor after performance status [12].

In 2010, a retrospective analysis of pooled data from five randomized, phase III of advanced NSCLC was done to investigate the role of sex and histology on efficacy, toxicity, and dose delivery after chemotherapy was given. Of 2349 patients, 34% were women. Women had a higher response rate to chemotherapy (42% versus 40%, P = 0.01) and longer survival than men (median OS 9.6 versus 8.6 months, P = 0.002). The difference in OS remained after adjusting for age, stage, performance status, and histology (hazard ratio 0.83, 95% confidence interval 0.74-0.92, P = 0.0005). Upon further examination, longer survival in women was only seen in patients with adenocarcinoma (test for interaction P = 0.006) [10].

In 2014 a study on 384 NSCLC patients investigated whether uric acid, the final breakdown product of purine metabolism in humans, has a prognostic significance in advanced NSCLC. Date of diagnosis, age, gender, performance status, smoking habit, weight loss within the past three years, disease stage, histological type of tumor, tumor diameter, area(s) of metastasis, number of metastasis, and the first-line treatment regimen of all patients were recorded. Serum uric acid levels were measured before first-line chemotherapy. Multivariate analysis showed that serum uric acid level (7.49 mg/dL) and poor performance status were independent prognostic factors (HR 3.18 95 % CI 1.36–6.41 and HR 2.18 95 % CI 1.18–3.21, respectively [11].

Another study was done to assess the prognostic role of neutrophilia, lymphocytopenia, and the neutrophil-to-lymphocyte ratio (NLR), in patients receiving first-line chemo- or targeted therapy for advanced non-small-cell lung cancer (NSCLC). They retrospectively analyzed 401 consecutive patients with advanced NSCLC treated with first-line chemo- or targeted therapy. Patients were stratified into two groups with pretreatment NLR ≥ 3.7 (Group A) vs. < 3.7 (Group B). The best NLR cut-off was identified by ROC curve analysis. A multivariate analysis, ECOG-PS≥2, stage IV cancer, non-adenocarcinoma histology, EGFR wild-type status, and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR status, and NLR≥3.7 were independent prognostic factors for worse PFS.13

In conclusion, male gender, poor Karnofsky performance status, age>70 years, low pretreatment Hb, Serum albumin levels, high NLR ≥ 3.7, high baseline serum uric acid level (>7.49 mg/dL), stage IV cancer, EGFR wild-type status, and squamous histology and presence of brain metastases are predictors of worse OS. Hence, this subset of patients should be counseled regarding the disease outcomes and offer the best palliative care, especially in resource-poor countries, to reduce the financial and over- investigation-related burden for such patients and their relatives.”